Neural stem cells are therapeutically effective donor cells for transplantation to treat severe neural dysfunctions caused by nerve injuries such as spinal cord injuries, and are thus promising for application in regenerative medicine (e.g., see, Okano H, Ogawa Y, Nakamura M, Kaneko S, Iwanami A, Toyama Y. (2003), Seminars in Cell & Developmental Biology 14(3): 191-198). For example, it has been considered to generate neural stem cells from undifferentiated cells such as embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells) (e.g., see, Okada Y, Matsumoto A, Shimazaki T, Enoki R, Koizumi A, Ishii S, Itoyama Y, Sobue G, Okano H. (2008), Stem Cells 2008 Dec. 26(12): 3086-3098) and transplant these cells into a patient. Clinical applications of ES cells have, however, problems on ethical concerns or rejections in transplantation, while induced pluripotent stem cells (iPS cells) still have some unsolved issues associated with, for example, canceration and still have many problems to be solved for therapeutic applications.
On the other hand, if neural stem cells residing in the brain of a living body can be activated and increased, neural dysfunctions are expected to be improved without any transplantation of neural stem cells from other individual. It can be thought that at least problems of rejections and canceration will not arise.
At present, however, growth factors and regulatory factors of cell lineage are major candidates that have been investigated as factors possibly being involved in the promotion of self-renewal or activation of neural stem cells, which have not yet been definitely identified. This means that the proliferation of the neural stem cells cannot necessarily be controlled artificially. To increase the number of endogenous neural stem cells is thus hard to achieve.
Accordingly, an object of the present invention is to provide agents for promoting the self-renewal of neural stem cells and a method of using the same.